Abstract
Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for, and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with 18F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) in head and neck cancer (HNC). Methods: 120 HNC patients underwent 0-30 min FMISO dPET in a customized immobilization mask, followed by 10 min static acquisitions starting at 93±6 and 160±13 min post-injection. A total of 248 lesions (≥2 cm3) were analyzed. Voxelwise pharmacokinetic modeling was conducted using an irreversible one-plasma two-tissue compartment model to calculate surrogate biomarkers of tumor hypoxia (k3), perfusion (K1) and FMISO distribution volume (DV). The analysis was repeated with truncated dPET datasets. Results: Substantial inter- and intra-tumor heterogeneity was observed for all investigated metrics. Equilibration between the blood and unbound FMISO was rapid in all tumors. FMISO distribution volume deviated from the expected value of unity, causing discrepancy between k3 maps and total FMISO uptake, and reducing the dynamic range of total FMISO uptake for quantifying the degree of hypoxia. Both positive and negative trends between hypoxia and perfusion were observed in individual lesions. All investigated metrics were reproducible when calculated from truncated 20-min dataset. Conclusion: FMISO dPET provides the data necessary to generate parametric maps of tumor hypoxia, perfusion and radiotracer distribution volume. These data clarify the ambiguity in interpreting FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20-min, facilitating the translation of FMISO dPET into the clinic.
- Oncology: Head and neck
- PET
- Radiotracer Tissue Kinetics
- 18F-fluoromisonidazole
- FMISO
- dynamic PET
- hypoxia
- perfusion
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.